Sustained and/or controlled release formulations provide convenient and efficacious methods of administering drugs to animals and humans. There are many advantages to the patient and clinician in extending the gastrointestinal transit time of orally administered controlled release formulations. Attempts have been made to prolong the residence time of sustained and/or controlled release formulations in the stomach by use of dosage materials in a buoyant form.
In such orally-administered sustained and/or controlled release preparations, the non-disintegrating dosage form preferably remains buoyant and freely floating in the gastric fluid for an extended period of time during which substantially all of the medicament contained therein is released into the stomach contents for absorption. For example, U.S. Pat. No. 3,901,232 to Michaels et al. and U.S. Pat. No. 4,055,178 to Harrigan describe the use of such dosage forms equipped with an inflatable chamber. U.S. Pat. No. 3,896,792 to Veil et al describes several coating techniques ensuring the buoyancy of a dosage form. U.S. Pat. No. 4,126,672 and U.S. Pat. No. 4,167,558 to Sheth et al. describe the formulation of hydrodynamically balanced systems, either capsules or tablets, having a bulk density less than one in contact with gastric fluid and remaining buoyant in the stomach.
Systems capable of measuring in vitro the floating force produced by a buoyant dosage form provide useful information as to certain critical characteristics of the products, which information aids in design, development and manufacturing of efficacious controlled release pharmaceutical products. For example, the time during which a capsule or a tablet remains buoyant in the stomach may determine, or at least have a significant effect upon, the amount of active ingredients absorbed and the rate at which the active ingredients will enter the bloodstream. Thus, the residence time of a buoyant dosage form in the stomach can be critical for those classes of active ingredients that are absorbed primarily from the stomach and are not suited to absorption during passage through the intestinal tract due to their physiochemical properties and/or favorable sites of absorption. There are also medicaments, e.g. antacids, which are intended to act in the stomach and lose beneficial properties when such medicaments pass too early into the intestinal tract. Hence, proper control of such residence-time floating duration in the stomach is important in both the design and the manufacturing of buoyant dosage forms.
As a dosage form releases a medicament contained therein, the bulk density and/or weight does not remain constant because during immersion such release is often accompanied by a modification of the weight and/or the volume of the material. Different dosage forms having the same floating duration may exhibit different floating characteristics in time. For example, buoyancy may range from high floating forces to low values close to sinking conditions and, in this last case, be more easily emptied from the stomach of the user. Determination of the floating force that will be developed by a dosage form during its buoyancy period is primarily an empirical exercise inasmuch as there are many intrinsic and extrinsic phenomena which modify the weight and/or the volume of the dosage form. Measurement of resultant weight when immersed as a function of time discloses the real floating characteristics of the product.
Important characteristics other than buoyancy may also be determined by measurement of resultant weight of an immersed material. For example, measurements using such systems provide data as to the melting of a fatty base suppository, the permeability of a film coating, the dissolution of an excipient, the solvation of a material, the erosion or the disintegration of a mass. Determination of such characteristics for a floating or a non-floating pharmaceutical dosage material by resultant-weight measurement, such as provided by the apparatus and method of the invention, enable also establishment of standard physical and/or chemical constants for a test material. Systems for determining such characteristics of a pharmaceutical dosage form may be classified generally as an "active" system, i.e., a system inducing dynamically a measurement and being often a destructive testing system, or as a "passive", i.e., a static measuring system operating in a non-destructive manner. An example of an active system is described in the publication of Washington et. al., Proceedings of the 45th Congress of the F.I.P., Montreal 1985, which shows an apparatus for applying an upwardly-directed pulling force to determine the point of breaking strength of a raft-forming antacid preparation immersed in a solvent. Another example of active system is provided by U.K. Patent No. 2,163,648 of Nippon Shinyaku which mentions a device for measuring the force required to make a floating dosage form sink.
It will be apparent to those skilled in the art of pharmaceutical tests and determinations, upon reading the hereinafter detailed description of the invention, that the present apparatus and method, for effecting resultant-weight measurements of a test object in an immersed condition within a fluid medium, is a "passive" measuring system, with regard to the previous discussion, and therefore differ from the hereabove exemplified "active" systems.
In addition and although the concept of weighing an immersed test material is known, no fully satisfactory "passive" measuring system of a continuous operating nature has been up to now described or proposed in the pharmaceutical technology literature or elsewhere for effecting resultant-weight measurements of various buoyant and non-buoyant pharmaceutical dosage materials, wholly or partially immersed in a solvent, or for determining a change, as a function of time, in a chemical and/or physical property of the material suspended in a fluid medium by measuring a change in a vertical force, acting on said material, under controlled and repeatable conditions.